Occurrence of Malignancy in Biopsy Specimens from Patients with Perforated Pre-pyloric Gastric Ulcers 

Occurrence of Malignancy in Biopsy Specimens from Patients with Perforated Pre-pyloric Gastric Ulcers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Occurrence of Malignancy in Biopsy Specimens from Patients with Perforated Pre-pyloric Gastric Ulcers Hadi Ahmadi Amoli, Soha Mohammadi, Nima Taghizadeh, Mohamadhosein Imanipour, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3850897/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Peptic ulcers, common digestive system disorders, often lead to perforation, which is associated with high mortality. Given the potential for underlying malignancy in gastric ulcers and perforations, this study focuses on assessing the frequency of cancer in gastric biopsies of patients with perforated pre-pyloric gastric ulcers. Methods This cross-sectional study involved 175 patients of all ages, both genders, with perforated pre-pyloric gastric ulcers in 2021–2022, who underwent emergency laparotomy surgery and with a definitive diagnosis of gastric ulcer perforation. A full-thickness sample was taken from the margin of the perforated pre-pyloric gastric ulcer for pathological examination to detect gastric malignancy. Results The patients' average age was 65.69 years, with a median of 65 years. All histopathological examinations of the gastric ulcer samples indicated benign conditions. Among the patients, 54.3% had a history of gastric ulcers, 37.7% had diabetes, 25.7% had hypertension, and 25.7% had both. Additionally, 1.7% suffered from chronic kidney failure, 1.1% from chronic liver failure, and 0.8% had other conditions like cardiovascular diseases. In total, 4.6% patients had a history of corticosteroid use, 66.9% patients had a history of NSAID use, and 58.9% patients had drug addiction. Conclusion Our study found no signs of cancer in the biopsies of patients with perforated pre-pyloric gastric ulcers; all cases showed benign pathology. This suggests that using gastric ulcer perforation alone as a reason for biopsy may need more investigation to ensure its accuracy and relevance. peptic ulcer perforation gastric ulcer peptic ulcer gastric cancer Introduction Peptic Ulcer Disease (PUD), characterized by inflammation in the inner lining of the stomach, the initial segment of the small intestine, or occasionally the lower section of the esophagus, is one of the most prevalent disorders affecting the digestive system, and its perforation carries the highest mortality rate (1). A duodenal ulcer is typically characterized by severe upper abdominal pain that improves after eating. In contrast, gastric ulcers can cause pain that worsens after eating, often described as a burning or dull ache. Additional symptoms may include bloating, vomiting, weight loss, or loss of appetite (2). About one-third of elderly individuals with gastric ulcers do not exhibit any symptoms. A variety of factors can cause complications in patients with PUD, including Helicobacter pylori (H. pylori) infection, non-steroidal anti-inflammatory drugs (NSAIDs), and low-dose aspirin. These factors can lead to complications, including bleeding, perforation, and stomach obstruction, with bleeding occurring in approximately 15% of cases (3, 4). Perforation, one of the most lethal complications associated with gastric ulcers, can develop in various locations, including the esophagus, stomach, duodenum, jejunum, and multiple segments of the small and large intestine (5). The inflammation and scarring resulting from gastric ulcers can further narrow the duodenum, resulting in symptoms of severe obstruction, vomiting, and sometimes hematoma formation. In certain cases, complications stemming from stomach ulcers can affect adjacent organs, giving rise to ulcers in the pancreas or liver (2, 6). Pre-pyloric ulcers have the highest perforation risk, followed by duodenal ulcers (5). The classic triad of abdominal pain, tachycardia, and abdominal rigidity characterizes gastric ulcer perforation (7). In many cases of PUD, surgical repair (either open or laparoscopic) may be necessary, although non-surgical approaches can be considered for selected patients (8). There can be a significant loss of fluid in patients with intestinal perforations. Depending on the type and volume of substances released from the digestive system, electrolyte imbalance can vary in severity. To minimize such disturbances, perforated patients require expeditious operative management (9). Regardless of the type of surgery employed for local control or definitive ulcer surgery, obtaining a biopsy from the ulcer margin is crucial in all cases of gastric perforation to rule out gastric carcinoma (10). The significant distinctions between stomach and duodenal ulcers significantly influence patients' surgical decisions. Notably, gastric ulcers may carry a risk of malignancy, underscoring the importance of complete ulcer excision or, at the very least, conducting a biopsy through an open surgical approach. Furthermore, patients with gastric ulcers are typically older and have a higher number of risk factors, which increases the postoperative mortality risk within this patient group (11, 12). Although less than 1% of gastric ulcers are premalignant, the relatively high incidence of cancer (9%) in cases of gastric perforation suggests that malignancy often underlies gastric ulcers in perforated patients (5). Given the elevated surgical risk associated with stomach ulcers, particularly in elderly individuals with multiple comorbidities, conducting a biopsy is crucial to confirm malignancy as the underlying cause (13). In our study, we performed biopsies on patients who arrived at the emergency room with clinical symptoms and approved diagnostic assessments suggesting a need for surgical intervention due to a perforated pre-pyloric gastric ulcer. During emergency surgery, we determined the frequency of confirmed malignancy by examining pathology reports derived from biopsies of the ulcer's wall, thus ensuring the diagnosis of a perforated pre-pyloric gastric ulcer. Material and Methods Study Design This study employed a cross-sectional conducted at Sina Hospital in Tehran between 2021 and 2022. The study included 175 patients of all ages, men and women, diagnosed with a perforated pre-pyloric gastric ulcer. To confirm the diagnosis of gastric perforation, all enrolled patients underwent emergency exploratory laparotomy surgery. All participants or their parents provided written informed consent. The study was approved by the ethics committee of Tehran University of Medical Sciences (ethics code IR.TUMS.SINAHOSPITAL.REC.1400.079), and followed the guidelines of the Helsinki Declaration and the Iranian Ministry of Health and Medical Education. Study Population The inclusion criteria consisted of patients diagnosed with perforated pre-pyloric gastric ulcers and with no indication of gross mass. Patients with ulcers in the antrum, near the lesser curvature, combined gastric and duodenal ulcer, and ulcer in the proximal stomach or cardia (High on lesser curvature) were excluded. Also, who had previously undergone distal gastrectomy surgery due to gastric perforation and those with a final diagnosis of perforated gastric cancer were excluded from the study. Additionally, patients with a proven history of gastric cancer or cases where the tumor was visible were excluded. Data Collection During the surgical procedures, full-thickness samples were obtained from the margin of the perforated prepyloric gastric ulcer. These biopsy samples of 175 patients, underwent pathological examination to assess the presence of gastric malignancy. In addition to pathological findings, histopathological analysis aimed to confirm the existence of malignancy in various forms, such as adenocarcinoma, lymphoma, or stromal tumors. Independent variables were collected, including demographic information (age, sex), medical history (previous gastric ulcer disease, diabetes, hypertension, chronic kidney disease, and liver failure), and drug history (daily and continuous use of NSAIDs and corticosteroids for at least 2 weeks) and the presence of drug addiction among patients. Data for these independent variables were gathered using a researcher-designed checklist administered during the patient's initial hospitalization. Data Analysis The data collected was entered into Excel software for initial preparation. Descriptive statistics were then applied to the data, including central indices (mean, median, and mode) for quantitative variables and dispersion indices (variance, standard deviation, range of changes, coefficient of variation). For qualitative data, the descriptive statistics included frequency, percentage, and prevalence. All necessary diagrams, such as a bar and pie chart, were generated. In the inferential statistics section, parametric tests, specifically the chi-square test, were employed to examine the study hypotheses after confirming the normality of the data distribution. Statistical analysis was conducted using SPSS software version 25, with a significance level of p < 0.05. Results In this study, we included 175 patients with perforated pre-pyloric gastric ulcers. All patients' gastric ulcer samples were reported to be benign in the histopathological findings, and no gross masses or tumors were detected, precluding a comparison of demographic and clinical variables with histopathological results. The average age of patients was 69.65 years, with a median of 65 years old and ages ranging from 50 to 81 years. A total of 57.1% of the patients were males, and 42.9% were females. The patients were nearly evenly divided by age, with 48.6% being 65 or younger and 51.4% older than 65. Additionally, 45.7% of patients had a history of gastric ulcers, whereas 54.3% did not (Table 1 ). Table 1 Patient demographic and clinical characteristics Characteristic Frequency Gender Male 100 (57.1) Female 75 (42.9) Age groups ≤ 65 85 (48.6) > 65 90 (51.4) History of Gastric Ulcer Reported 80 (45.7) Not Reported 95 (54.3) Medical History Diabetes 66 (37.7) Hypertension 45 (25.7) Both Diabetes and Hypertension 45 (25.7) Chronic Kidney Disease 3 (1.7) Chronic Liver Failure 2 (1.1) Other Illnesses (e.g., Cardiovascular, Respiratory) 14 (8) n =175 ; data are presented as number (%) In assessing accompanying underlying diseases, we found that 37.7% of patients had diabetes, 25.7% had hypertension, and 25.7% had both diabetes and hypertension. 8% of patients mentioned other diseases like cardiovascular, respiratory conditions, and rheumatism (Table 1 ). Regarding the frequency and percentage of histories of corticosteroid use, NSAIDs, and addiction among study patients, 4.6% had a history of corticosteroid use, 66.9% had used NSAIDs, and 58.9% had a history of drug addiction (Table 2 ). Table 2 Patient’s drug history Characteristic Total Drug History History of Corticosteroid Use No 167 (95.4) Yes 8 (4.57) History of NSAIDs Use No 58 (33.1) Yes 117 (66.9) Substance Abuse (Drug Addiction) No 72 (41.1) Yes 103 (58.9) n =175 ; data are preesented as number (%) No significant differences were observed in comparing co-morbidities between men and women, as shown in Table 3 . Also, there was no significant difference between men and women regarding gastric ulcer history, corticosteroids, and NSAID usage. However, the prevalence of drug addiction was significantly higher in men than in women (P < 0.001) (Table 3 ). Table 3 Comparison of medical conditions and drug histories between genders Variable Male Female P-value* Medical Conditions Diabetes 63 (56.8) 48 (43.2) 0.892 Hypertension 51 (56.7) 39 (43.3) 0.896 Chronic Kidney Disease 1 (33.3%) 2 (66.7) 0.401 Chronic Liver Failure 2 (100%) - 0.218 Previous Ulcer History 45 (56.3%) 35 (43.8%) 0.827 Drug History Corticosteroid 4 (50.0%) 4 (50.0%) 0.676 NSAIDs 60 (51.3%) 57 (48.7%) 0.261 Substance Abuse (Drug Addiction) 96 (93.2%) 7 (6.8%) < 0.001 pearson chi-square test; data are preesented as frequency (%); * p < 0.05 In the comparison of underlying diseases between the two age groups, the frequency of diabetes and hypertension was significantly higher in patients over 65 years (P = 0.005 and P = 0.008, respectively). No significant differences were found in chronic kidney disease and liver failure frequency between the two age groups. The prevalence of a previous history of gastric ulcers was significantly higher in the over-65 age group (P < 0.001). Lastly, there was no statistically significant difference in the history of corticosteroid use, NSAID use, or drug addiction between the under and over-65 age groups (Table 4 ). Table 4 Comparison of underlying diseases and drug histories between age groups Variables ≤ 65 years > 65 years P-value* Medical Conditions Diabetes 45 (40.5) 66 (59.5) 0.005 Hypertension 35 (38.9) 55 (61.1) 0.008 Chronic Kidney Failure 2 (66.7) 1 (33.3) 0.527 Chronic Liver Failure - 2 (100) 0.167 Previous Ulcer History 24 (30.0) 56 (70.0) < 0.001 Drug History Corticosteroid 2 (25.0) 6 (75.0) 0.172 NSAIDs 61 (52.1) 56 (47.9) 0.180 Substance Abuse (Drug Addiction) 51 (49.8) 52 (50.5) 0.765 Pearson chi-square test data are presented as frequency (%); * p < 0.05 Discussion Digestive system malignancies are among the deadliest cancers worldwide and are closely linked with chronic inflammation (14). Stomach ulcers significantly contribute to these malignancies. Although biopsies are commonly used in perforated gastric ulcers in the pre-pyloric region, our study indicates a potential need to revise this strategy. A key finding is the absence of malignancy and gross mass or tumor in gastric biopsies from patients with perforated pre-pyloric stomach ulcers, all showing benign pathology. This raises the question of whether biopsies are necessary for all cases, as accurate malignancy diagnosis in gastric biopsies requires a minimum of 8 samples from various parts of the lesion (15). Our research is among the few studies that examine malignancy rates in patients with perforated gastric ulcers. Comparing these findings with other studies is challenging due to the focus on peptic ulcer risk factors in other studies. Due to this finding, the relationship between perforation and demographic or clinical variables couldn't be explored. However, chronic inflammation caused by Helicobacter pylori in patients with perforated peptic ulcers remains a significant medical concern in gastric cancer development (16). In the context of the relationship between H. pylori infections and gastric diseases, the comprehensive meta-analysis by Shirani et al. (17) is particularly enlightening. This study, encompassing 149 studies with a massive sample size of 352,872 individuals, delves into the global prevalence of gastric cancer among H. pylori-infected persons. Through extensive data extraction and statistical analysis, it sheds light on the prevalence and characteristics of gastric cancer in those afflicted with H. pylori. A vital aspect of this relationship is the role of specific bacterial features in causing cancer. Notably, certain H. pylori strains produce a toxin named CagA. Once injected into stomach lining cells, this toxin can induce carcinogenic changes, promoting cell growth and motility, leading to chronic inflammation. Epidemiological studies underscore that strains positive for CagA are more strongly associated with non-cardia gastric cancer than CagA-negative strains. Lifestyle factors also influence the risk of H. pylori-induced stomach cancer. Smokers infected with H. pylori, for instance, face a higher risk of developing stomach cancer compared to non-smokers with the infection (18). Additionally, diets high in salt and processed meats are linked to an increased risk of stomach cancer, potentially exacerbating H. pylori colonization and CagA entry into gastric cells (19, 20). Although our study did not evaluate lifestyle factors such as smoking, salt intake, and meat consumption, these aspects are crucial in understanding the overall risk landscape for gastric cancer in H. pylori-infected individuals. Therefore, it was essential to consider these factors alongside the biological characteristics of H. pylori and its interaction with gastric pathology. In our study, gastric ulcer perforation was more common in men than women, with the incidence of gastric ulcer perforation being 1.3 times higher in men. Comparatively, Bhattarai et al.'s (21) study found a 1.9 times greater prevalence of gastric malignancies in men than women. Similarly, Ramakrishnan et al. (22) reported the ratio to be 2 times higher in men. In their study, Hearnshaw et al. (23) also reported that the incidence of upper gastrointestinal bleeding in men was twice as high as in women across all age groups. The higher incidence of stomach ulcers in men compared to women may be attributed to men's greater consumption of cigarettes and drugs. Patients' average age at the time of gastric ulcer perforation was 65.7 years. Cheung et al. (24) noted that age, particularly between 60 and 79 years, is a predisposing factor for peptic ulcer perforation. In industrialized countries, the prevalence of Helicobacter pylori infection, followed by gastric ulcers, increases with age. This long-term inflammatory response against H. pylori in the gastric mucosa of older individuals may lead to permanent tissue damage, potentially laying the basis for gastric cancer (25, 26). The review by Alexander et al. (27) posits that the pathogenesis of gastric ulcers and gastric cancer is influenced not just by the presence of H. pylori, but also by the complex interplay of its virulence factors, the host's immune response, and the gastrointestinal microbiome. Our study findings revealed that 4.5% of patients had a history of continuous corticosteroid use for at least two weeks. Corticosteroid treatment is associated with an increased risk of gastrointestinal side effects such as gastritis, ulcers, and gastrointestinal bleeding. The estimated relative risk increase for gastrointestinal side effects with corticosteroid alone varies between 1.1 and 1.5 times accroding to Liu et al’s study. Concurrent use of corticosteroids and NSAIDs notably increases gastrointestinal event risks (28). Another finding of our research is that 67% of patients with perforated gastric ulcers had been taking NSAIDs. The excessive use of NSAIDs in these patients can be attributed to an increase in musculoskeletal pain and cardiovascular diseases associated with aging (refer to Table 2 ). NSAIDs have been identified as a potential risk factor for mortality following upper gastrointestinal bleeding, primarily caused by peptic ulcers, in various studies, including those by Sibilia and colleagues (29), Ben-Menachem and colleagues (30), and Straube and colleagues (31). However, Wu et al.'s study (32), involving 52,161 patients, revealed that regular NSAID use, particularly in patients with H. pylori-associated gastric ulcers, significantly lowered the risk of gastric cancer. This was evident in their observation that patients who never used NSAIDs had a higher risk of gastric cancer, while regular NSAID users showed a notably reduced risk. This is in line with our study's result; our study found that 66.9% of patients with perforated stomach ulcers were NSAID users, and importantly, none of these patients exhibited signs of malignancy in their gastric biopsies. This absence of malignancy in NSAID users with gastric ulcers aligns with and supports Wu et al.'s findings, suggesting a protective role of NSAIDs against the development of gastric cancer, especially in the context of H. pylori infection. In contrast, Li et al. (33) explored the impact of non-aspirin (NA-NSAIDs) on gastric cancer development in a large cohort of over 92,000 H. pylori-infected patients who had undergone H. pylori eradication therapy. This large-scale, territory-wide study used a time-dependent analysis to address potential biases. Contrary to previous meta-analyses that suggested a beneficial effect of NSAIDs (including both aspirin and NA-NSAIDs) on gastric cancer prevention, this study found that the use of NA-NSAIDs was not associated with a decreased risk of developing gastric cancer. This finding presents a contrasting perspective to the commonly held view of NSAIDs' protective role in gastric cancer development. Interestingly, 59% of patients with gastric ulcer perforation had a history of substance abuse. The study by Salemi et al. (34) also has shown a significant link between peptic ulcers and smoking. It seems that the mechanisms of tobacco and drug use in causing peptic ulcers are similar, and the continuation of these habits may lead to ulcer perforation. Smoking increases acid production and decreases bicarbonate and prostaglandin production, according to Ramakrishnan et al. (22). This can delay the healing of duodenal and gastric ulcers. In a study by Paragomi et al. (35) which investigated the association between PUD and Gastric Cancer by incorporating data from 11 case-control studies within their consortium, a significant link was established between gastric ulcers and an elevated risk of gastric cancer. However, no such association was observed with duodenal ulcers. Notably, it is essential to consider that pre-pyloric ulcers, a subtype of GU, carry the highest risk of perforation. Furthermore, the higher risk of non-cardia GC in patients with GU underscores the importance of specific and accurate diagnostic methods such as biopsy or gastroscopy, especially in cases with gastric ulcers. While our study did not investigate the location of the ulcer or the number of biopsy samples, these aspects could pave the way for future research. The decision to perform a biopsy can be made based on the doctor's preference, the patient's condition, and the availability of resources. Conclusions In this study, we exclusively examined patients with perforated pre-pyloric gastric ulcers and found no evidence of malignancy or gross masses in the collected samples. These findings suggest that biopsy procedures may be unnecessary for patients presenting with pre-pyloric gastric ulcers in the absence of any indicators of malignancy or noticeable masses. Therefore, we recommend more selective criteria for biopsies in future studies, potentially reducing the number of unnecessary invasive procedures for patients with similar presentations. Research Limitations The duration of gastric ulcer affliction was not examined and the study did not investigate cigarette smoking diet habits and presence of H. pylori. Recommendations for Future Research It's suggested that a study be conducted to explore the risk factors for perforation in patients with gastric ulcers. Given the number of samples in this study, it is recommended that future research involve more extensive sample sizes and include follow-up of patients after treatment and the healing of perforated ulcers. Declarations Ethics approval The study was approved by the ethics committee of Tehran University of Medical Sciences (TUMS) (ethics code IR.TUMS.SINAHOSPITAL.REC.1400.079.), and followed the guidelines of the Helsinki Declaration and the Iranian Ministry of Health and Medical Education. Consent to participate Informed consent was obtained from all individual participants included in the study. Consent for publication The participants have given their consent for the publication of their data and study findings. Availability of data and materials The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Funding This study was conducted without any funding or involvement from external sources. Author contributions All authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by Hadi Ahmadi Amoli, Mohamadhosein Imanipour, and Reza Hajebi. The first draft and main text of the manuscript was written and revised critically by Soha Mohammadi and Nima Taghizadeh, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgments We would like to acknowledge the contributions and support provided by medical and nursing staff of Sina hospital who have assisted in various aspects of this research. References Ergul E, Gozetlik EO. Emergency spontaneous gastric perforations: ulcus versus cancer. Langenbeck's archives of surgery . 2009;394:643-646. Ravisankar P, Koushik O, Reddy A, KumarU AP, Pragna P. A detailed analysis on acidity and ulcers in esophagus, gastric and duodenal ulcers and management. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) . 2016;15(1):94-114. Tarasconi A, Coccolini F, Biffl WL, et al. Perforated and bleeding peptic ulcer: WSES guidelines. World Journal of Emergency Surgery . 2020;15(1):1-24. Ahmed M, Mansoor T, Rab AZ, Rizvi SAA. Risk factors influencing postoperative outcome in patients with perforated peptic ulcer: a prospective cohort study. European Journal of Trauma and Emergency Surgery . 2022:1-6. Weledji EP. An overview of gastroduodenal perforation. Frontiers in Surgery . 2020;7:573901. Abbass A, Khalid S, Boppana V, Hanson J, Lin H, McCarthy D. Giant gastric ulcers: an unusual culprit. Digestive Diseases and Sciences . 2020;65:2811-2817. Anania G, Campagnaro A, Marchetti F, Resta G, Cirocchi R. Perforated Gastroduodenal Ulcer. 2021:129-139. Karabulut K, Dinçer M, Liman RK, Usta S. Non-operative management of perforated peptic ulcer: A single-center experience. Ulus Travma Acil Cerrahi Derg . 2019;25(6):585-588. Pouli S, Kozana A, Papakitsou I, Daskalogiannaki M, Raissaki M. Gastrointestinal perforation: clinical and MDCT clues for identification of aetiology. Insights into Imaging . 2020;11(1):1-19. Ali A, Ahmed BH, Nussbaum MS. Surgery for peptic ulcer disease. Shackelford's Surgery of the Alimentary Tract, 2 Volume Set . Elsevier; 2019:673-701. Felder SI, Barmparas G, Murrell Z, Fleshner P. Risk factors for failure of percutaneous drainage and need for reoperation following symptomatic gastrointestinal anastomotic leak. Am J Surg . Jul 2014;208(1):58-64. doi:10.1016/j.amjsurg.2013.08.050 Kumarasinghe MP, Bourke MJ, Brown I, et al. Pathological assessment of endoscopic resections of the gastrointestinal tract: a comprehensive clinicopathologic review. Modern Pathology . 2020;33(6):986-1006. Wan JJ, Fei SJ, Lv SX, et al. Role of gastroscopic biopsy of gastric ulcer margins and healed sites in the diagnosis of early gastric cancer: A clinical controlled study of 513 cases. Oncol Lett . Oct 2018;16(4):4211-4218. doi:10.3892/ol.2018.9156 Marusawa H, Jenkins BJ. Inflammation and gastrointestinal cancer: an overview. Cancer Lett . Apr 10 2014;345(2):153-6. doi:10.1016/j.canlet.2013.08.025 Sancho-Poch F, Balanzo J, Ocana J, et al. An evaluation of gastric biopsy in the diagnosis of gastric cancer. Gastrointestinal endoscopy . 1978;24(6):281-282. Yang H, Wei B, Hu B. Chronic inflammation and long-lasting changes in the gastric mucosa after Helicobacter pylori infection involved in gastric cancer. Inflammation Research . 2021:1-12. Shirani M, Pakzad R, Haddadi MH, et al. The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis. BMC Infectious Diseases . 2023;23(1):543. Butt J, Varga MG, Wang T, et al. Smoking, Helicobacter Pylori Serology, and Gastric Cancer Risk in Prospective Studies from China, Japan, and Korea. Cancer Prev Res (Phila) . Oct 2019;12(10):667-674. doi:10.1158/1940-6207.Capr-19-0238 Wang XQ, Terry PD, Yan H. Review of salt consumption and stomach cancer risk: epidemiological and biological evidence. World J Gastroenterol . May 14 2009;15(18):2204-13. doi:10.3748/wjg.15.2204 Gaddy JA, Radin JN, Loh JT, et al. High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis. Infect Immun . Jun 2013;81(6):2258-67. doi:10.1128/iai.01271-12 Bhattarai S, Gyawali M, Regmi S. Prevalence of Gastric Cancers among Patients Undergoing Upper Gastrointestinal Endoscopies in a Tertiary Care Hospital in Nepal: A Descriptive Cross-sectional Study. JNMA J Nepal Med Assoc . Jan 31 2021;59(233):65-68. doi:10.31729/jnma.5657 Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician . Oct 1 2007;76(7):1005-12. Hearnshaw SA, Logan RF, Lowe D, Travis SP, Murphy MF, Palmer KR. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. Gut . Oct 2011;60(10):1327-35. doi:10.1136/gut.2010.228437 Cheung J, Rajala J, Moroz D, Zhu Q, Stamm M, Sandha GS. Acetylsalicylic acid use in patients with acute myocardial infarction and peptic ulcer bleeding. Can J Gastroenterol . Sep 2009;23(9):619-23. doi:10.1155/2009/509258 Kumar S, Kumar A, Dixit VK. Direct detection and analysis of vacA genotypes and cagA gene of Helicobacter pylori from gastric biopsies by a novel multiplex polymerase chain reaction assay. Diagn Microbiol Infect Dis . Dec 2008;62(4):366-73. doi:10.1016/j.diagmicrobio.2008.07.014 Piazuelo MB, Correa P. Gastric cáncer: Overview. Colomb Med (Cali) . Jul 2013;44(3):192-201. Alexander SM, Retnakumar RJ, Chouhan D, et al. Helicobacter pylori in Human Stomach: The Inconsistencies in Clinical Outcomes and the Probable Causes. Front Microbiol . 2021;12:713955. doi:10.3389/fmicb.2021.713955 Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol . Aug 15 2013;9(1):30. doi:10.1186/1710-1492-9-30 Sibilia J, Ravaud P, Marck G. [Digestive and hemorrhage complications of low-dose aspirin]. Presse Med . Nov 22 2003;32(37 Pt 2):S17-28. Les complications digestives et hémorragiques de l'aspirine à faible dose. Ben-Menachem T, Dominitz JA. Acute upper gastrointestinal hemorrhage in an elderly woman taking aspirin and clopidogrel. Clin Gastroenterol Hepatol . Aug 2011;9(8):649-52. doi:10.1016/j.cgh.2011.03.022 Straube S, Tramèr MR, Moore RA, Derry S, McQuay HJ. Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. BMC Gastroenterol . Jun 5 2009;9:41. doi:10.1186/1471-230x-9-41 Wu CY, Wu MS, Kuo KN, Wang CB, Chen YJ, Lin JT. Effective reduction of gastric cancer risk with regular use of nonsteroidal anti-inflammatory drugs in Helicobacter pylori-infected patients. J Clin Oncol . Jun 20 2010;28(18):2952-7. doi:10.1200/jco.2009.26.0695 Li B, Cheung KS, Wong IY, Leung WK, Law S. Nonaspirin nonsteroidal anti-inflammatory drugs and gastric cancer risk after Helicobacter pylori eradication: A territory-wide study. Cancer . Jun 1 2021;127(11):1805-1815. doi:10.1002/cncr.33412 Salemi Z, Kamali Pooya S, Ghasemi M. Secretor Status and Some Risk Factors in Duodenal Ulcer, Gastric Ulcer, and Gastric Cancer. Original Atricle. Journal of Arak University of Medical Sciences . 2013;16(3):0-0. Paragomi P, Dabo B, Pelucchi C, et al. The Association between Peptic Ulcer Disease and Gastric Cancer: Results from the Stomach Cancer Pooling (StoP) Project Consortium. Cancers (Basel) . Oct 7 2022;14(19)doi:10.3390/cancers14194905 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3850897","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":266368034,"identity":"379523e9-f49b-45d9-b65d-d37bb649e691","order_by":0,"name":"Hadi Ahmadi Amoli","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hadi","middleName":"Ahmadi","lastName":"Amoli","suffix":""},{"id":266368035,"identity":"cd0fecd7-df2f-4396-878c-be652b065492","order_by":1,"name":"Soha Mohammadi","email":"","orcid":"","institution":"Iran University of Medical Sciences (IUMS)","correspondingAuthor":false,"prefix":"","firstName":"Soha","middleName":"","lastName":"Mohammadi","suffix":""},{"id":266368036,"identity":"a8aacf1f-8b35-438d-ba98-3e068fdbb9fa","order_by":2,"name":"Nima Taghizadeh","email":"","orcid":"","institution":"Iran University of Medical Sciences (IUMS)","correspondingAuthor":false,"prefix":"","firstName":"Nima","middleName":"","lastName":"Taghizadeh","suffix":""},{"id":266368037,"identity":"6b774e3a-97cf-4ae8-a666-4706eae35e5e","order_by":3,"name":"Mohamadhosein Imanipour","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohamadhosein","middleName":"","lastName":"Imanipour","suffix":""},{"id":266368038,"identity":"dcbbdb92-b87d-455f-8f0f-b44b05168a0b","order_by":4,"name":"Reza Hajebi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYLACxgYGZgYJxsYHHxgYEkjS0mw4gxQtDAwSDGzSPMRoMW9vf/iBcYcdO790c4O0bZtdHj97A+OHjzm4tcicOZAswXgmmVlyzsEG49y25GLJngPMkjO34dYiIZFwQIKxjZnZ4EZiQ3JuG3PihhsJbMy8+LTIP2z+wdhWz2wP1HLYsq2eCC0SzGxAWw4zG0gkNjYDGURo4Uljs2BsO84scedgM2PPueOJM3sONuP3C/vxxzcY26qT+We3P//xo6w6sZ+9+eCHj3i0gADzHwaGZDCLkQ1MNuBXDwV2EOoPUYpHwSgYBaNghAEA9UVQvyum/f4AAAAASUVORK5CYII=","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Reza","middleName":"","lastName":"Hajebi","suffix":""}],"badges":[],"createdAt":"2024-01-10 16:29:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3850897/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3850897/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49574201,"identity":"5b665a34-df46-4844-b4c2-5af8aacd9094","added_by":"auto","created_at":"2024-01-13 21:07:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":328091,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3850897/v1/a501f542-b25a-446b-bb6d-1cbb7ca5ac66.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Occurrence of Malignancy in Biopsy Specimens from Patients with Perforated Pre-pyloric Gastric Ulcers ","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePeptic Ulcer Disease (PUD), characterized by inflammation in the inner lining of the stomach, the initial segment of the small intestine, or occasionally the lower section of the esophagus, is one of the most prevalent disorders affecting the digestive system, and its perforation carries the highest mortality rate (1). A duodenal ulcer is typically characterized by severe upper abdominal pain that improves after eating. In contrast, gastric ulcers can cause pain that worsens after eating, often described as a burning or dull ache. Additional symptoms may include bloating, vomiting, weight loss, or loss of appetite (2). About one-third of elderly individuals with gastric ulcers do not exhibit any symptoms. A variety of factors can cause complications in patients with PUD, including Helicobacter pylori (H. pylori) infection, non-steroidal anti-inflammatory drugs (NSAIDs), and low-dose aspirin. These factors can lead to complications, including bleeding, perforation, and stomach obstruction, with bleeding occurring in approximately 15% of cases (3, 4).\u003c/p\u003e \u003cp\u003ePerforation, one of the most lethal complications associated with gastric ulcers, can develop in various locations, including the esophagus, stomach, duodenum, jejunum, and multiple segments of the small and large intestine (5). The inflammation and scarring resulting from gastric ulcers can further narrow the duodenum, resulting in symptoms of severe obstruction, vomiting, and sometimes hematoma formation. In certain cases, complications stemming from stomach ulcers can affect adjacent organs, giving rise to ulcers in the pancreas or liver (2, 6).\u003c/p\u003e \u003cp\u003ePre-pyloric ulcers have the highest perforation risk, followed by duodenal ulcers (5). The classic triad of abdominal pain, tachycardia, and abdominal rigidity characterizes gastric ulcer perforation (7). In many cases of PUD, surgical repair (either open or laparoscopic) may be necessary, although non-surgical approaches can be considered for selected patients (8). There can be a significant loss of fluid in patients with intestinal perforations. Depending on the type and volume of substances released from the digestive system, electrolyte imbalance can vary in severity. To minimize such disturbances, perforated patients require expeditious operative management (9).\u003c/p\u003e \u003cp\u003eRegardless of the type of surgery employed for local control or definitive ulcer surgery, obtaining a biopsy from the ulcer margin is crucial in all cases of gastric perforation to rule out gastric carcinoma (10). The significant distinctions between stomach and duodenal ulcers significantly influence patients' surgical decisions. Notably, gastric ulcers may carry a risk of malignancy, underscoring the importance of complete ulcer excision or, at the very least, conducting a biopsy through an open surgical approach. Furthermore, patients with gastric ulcers are typically older and have a higher number of risk factors, which increases the postoperative mortality risk within this patient group (11, 12).\u003c/p\u003e \u003cp\u003eAlthough less than 1% of gastric ulcers are premalignant, the relatively high incidence of cancer (9%) in cases of gastric perforation suggests that malignancy often underlies gastric ulcers in perforated patients (5). Given the elevated surgical risk associated with stomach ulcers, particularly in elderly individuals with multiple comorbidities, conducting a biopsy is crucial to confirm malignancy as the underlying cause (13). In our study, we performed biopsies on patients who arrived at the emergency room with clinical symptoms and approved diagnostic assessments suggesting a need for surgical intervention due to a perforated pre-pyloric gastric ulcer. During emergency surgery, we determined the frequency of confirmed malignancy by examining pathology reports derived from biopsies of the ulcer's wall, thus ensuring the diagnosis of a perforated pre-pyloric gastric ulcer.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis study employed a cross-sectional conducted at Sina Hospital in Tehran between 2021 and 2022. The study included 175 patients of all ages, men and women, diagnosed with a perforated pre-pyloric gastric ulcer. To confirm the diagnosis of gastric perforation, all enrolled patients underwent emergency exploratory laparotomy surgery.\u003c/p\u003e \u003cp\u003e All participants or their parents provided written informed consent. The study was approved by the ethics committee of Tehran University of Medical Sciences (ethics code IR.TUMS.SINAHOSPITAL.REC.1400.079), and followed the guidelines of the Helsinki Declaration and the Iranian Ministry of Health and Medical Education.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eThe inclusion criteria consisted of patients diagnosed with perforated pre-pyloric gastric ulcers and with no indication of gross mass. Patients with ulcers in the antrum, near the lesser curvature, combined gastric and duodenal ulcer, and ulcer in the proximal stomach or cardia (High on lesser curvature) were excluded. Also, who had previously undergone distal gastrectomy surgery due to gastric perforation and those with a final diagnosis of perforated gastric cancer were excluded from the study. Additionally, patients with a proven history of gastric cancer or cases where the tumor was visible were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eDuring the surgical procedures, full-thickness samples were obtained from the margin of the perforated prepyloric gastric ulcer. These biopsy samples of 175 patients, underwent pathological examination to assess the presence of gastric malignancy. In addition to pathological findings, histopathological analysis aimed to confirm the existence of malignancy in various forms, such as adenocarcinoma, lymphoma, or stromal tumors. Independent variables were collected, including demographic information (age, sex), medical history (previous gastric ulcer disease, diabetes, hypertension, chronic kidney disease, and liver failure), and drug history (daily and continuous use of NSAIDs and corticosteroids for at least 2 weeks) and the presence of drug addiction among patients. Data for these independent variables were gathered using a researcher-designed checklist administered during the patient's initial hospitalization.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eThe data collected was entered into Excel software for initial preparation. Descriptive statistics were then applied to the data, including central indices (mean, median, and mode) for quantitative variables and dispersion indices (variance, standard deviation, range of changes, coefficient of variation). For qualitative data, the descriptive statistics included frequency, percentage, and prevalence. All necessary diagrams, such as a bar and pie chart, were generated. In the inferential statistics section, parametric tests, specifically the chi-square test, were employed to examine the study hypotheses after confirming the normality of the data distribution. Statistical analysis was conducted using SPSS software version 25, with a significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, we included 175 patients with perforated pre-pyloric gastric ulcers. All patients' gastric ulcer samples were reported to be benign in the histopathological findings, and no gross masses or tumors were detected, precluding a comparison of demographic and clinical variables with histopathological results.\u003c/p\u003e \u003cp\u003eThe average age of patients was 69.65 years, with a median of 65 years old and ages ranging from 50 to 81 years. A total of 57.1% of the patients were males, and 42.9% were females. The patients were nearly evenly divided by age, with 48.6% being 65 or younger and 51.4% older than 65. Additionally, 45.7% of patients had a history of gastric ulcers, whereas 54.3% did not (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient demographic and clinical characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (57.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (42.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge groups\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le; 65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85 (48.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt; 65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (51.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of Gastric Ulcer\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 (45.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (54.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedical History\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (37.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (25.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth Diabetes and Hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (25.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Kidney Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Liver Failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Illnesses (e.g., Cardiovascular, Respiratory)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003en =175\u0026nbsp;; data are presented as number (%)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn assessing accompanying underlying diseases, we found that 37.7% of patients had diabetes, 25.7% had hypertension, and 25.7% had both diabetes and hypertension. 8% of patients mentioned other diseases like cardiovascular, respiratory conditions, and rheumatism (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegarding the frequency and percentage of histories of corticosteroid use, NSAIDs, and addiction among study patients, 4.6% had a history of corticosteroid use, 66.9% had used NSAIDs, and 58.9% had a history of drug addiction (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient\u0026rsquo;s drug history\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eDrug History\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHistory of Corticosteroid Use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e167 (95.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (4.57)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHistory of NSAIDs Use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (33.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e117 (66.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSubstance Abuse (Drug Addiction)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (41.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (58.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003csup\u003en =175\u0026nbsp;; data are preesented as number (%)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNo significant differences were observed in comparing co-morbidities between men and women, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Also, there was no significant difference between men and women regarding gastric ulcer history, corticosteroids, and NSAID usage. However, the prevalence of drug addiction was significantly higher in men than in women (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of medical conditions and drug histories between genders\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP-value*\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eMedical Conditions\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (56.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (43.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.892\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (56.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.896\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Kidney Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Liver Failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious Ulcer History\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (56.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.827\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDrug History\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.676\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNSAIDs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (51.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (48.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.261\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubstance Abuse (Drug Addiction)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96 (93.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003epearson chi-square test; data are preesented as frequency (%); * p \u0026lt; 0.05\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the comparison of underlying diseases between the two age groups, the frequency of diabetes and hypertension was significantly higher in patients over 65 years (P\u0026thinsp;=\u0026thinsp;0.005 and P\u0026thinsp;=\u0026thinsp;0.008, respectively). No significant differences were found in chronic kidney disease and liver failure frequency between the two age groups. The prevalence of a previous history of gastric ulcers was significantly higher in the over-65 age group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Lastly, there was no statistically significant difference in the history of corticosteroid use, NSAID use, or drug addiction between the under and over-65 age groups (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of underlying diseases and drug histories between age groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;65 years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;65 years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP-value*\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eMedical Conditions\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (40.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Kidney Failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.527\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Liver Failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious Ulcer History\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (30.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDrug History\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNSAIDs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (47.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubstance Abuse (Drug Addiction)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (49.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (50.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003csub\u003ePearson chi-square test\u003c/sub\u003e\u003c/p\u003e \u003cp\u003e\u003csup\u003edata are presented as frequency (%); * p \u0026lt; 0.05\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDigestive system malignancies are among the deadliest cancers worldwide and are closely linked with chronic inflammation (14). Stomach ulcers significantly contribute to these malignancies. Although biopsies are commonly used in perforated gastric ulcers in the pre-pyloric region, our study indicates a potential need to revise this strategy.\u003c/p\u003e \u003cp\u003eA key finding is the absence of malignancy and gross mass or tumor in gastric biopsies from patients with perforated pre-pyloric stomach ulcers, all showing benign pathology. This raises the question of whether biopsies are necessary for all cases, as accurate malignancy diagnosis in gastric biopsies requires a minimum of 8 samples from various parts of the lesion (15). Our research is among the few studies that examine malignancy rates in patients with perforated gastric ulcers. Comparing these findings with other studies is challenging due to the focus on peptic ulcer risk factors in other studies.\u003c/p\u003e \u003cp\u003eDue to this finding, the relationship between perforation and demographic or clinical variables couldn't be explored. However, chronic inflammation caused by Helicobacter pylori in patients with perforated peptic ulcers remains a significant medical concern in gastric cancer development (16). In the context of the relationship between H. pylori infections and gastric diseases, the comprehensive meta-analysis by Shirani et al. (17) is particularly enlightening. This study, encompassing 149 studies with a massive sample size of 352,872 individuals, delves into the global prevalence of gastric cancer among H. pylori-infected persons. Through extensive data extraction and statistical analysis, it sheds light on the prevalence and characteristics of gastric cancer in those afflicted with H. pylori. A vital aspect of this relationship is the role of specific bacterial features in causing cancer. Notably, certain H. pylori strains produce a toxin named CagA. Once injected into stomach lining cells, this toxin can induce carcinogenic changes, promoting cell growth and motility, leading to chronic inflammation. Epidemiological studies underscore that strains positive for CagA are more strongly associated with non-cardia gastric cancer than CagA-negative strains.\u003c/p\u003e \u003cp\u003eLifestyle factors also influence the risk of H. pylori-induced stomach cancer. Smokers infected with H. pylori, for instance, face a higher risk of developing stomach cancer compared to non-smokers with the infection (18). Additionally, diets high in salt and processed meats are linked to an increased risk of stomach cancer, potentially exacerbating H. pylori colonization and CagA entry into gastric cells (19, 20). Although our study did not evaluate lifestyle factors such as smoking, salt intake, and meat consumption, these aspects are crucial in understanding the overall risk landscape for gastric cancer in H. pylori-infected individuals. Therefore, it was essential to consider these factors alongside the biological characteristics of H. pylori and its interaction with gastric pathology.\u003c/p\u003e \u003cp\u003eIn our study, gastric ulcer perforation was more common in men than women, with the incidence of gastric ulcer perforation being 1.3 times higher in men. Comparatively, Bhattarai et al.'s (21) study found a 1.9 times greater prevalence of gastric malignancies in men than women. Similarly, Ramakrishnan et al. (22) reported the ratio to be 2 times higher in men. In their study, Hearnshaw et al. (23) also reported that the incidence of upper gastrointestinal bleeding in men was twice as high as in women across all age groups. The higher incidence of stomach ulcers in men compared to women may be attributed to men's greater consumption of cigarettes and drugs.\u003c/p\u003e \u003cp\u003ePatients' average age at the time of gastric ulcer perforation was 65.7 years. Cheung et al. (24) noted that age, particularly between 60 and 79 years, is a predisposing factor for peptic ulcer perforation. In industrialized countries, the prevalence of Helicobacter pylori infection, followed by gastric ulcers, increases with age. This long-term inflammatory response against H. pylori in the gastric mucosa of older individuals may lead to permanent tissue damage, potentially laying the basis for gastric cancer (25, 26). The review by Alexander et al. (27) posits that the pathogenesis of gastric ulcers and gastric cancer is influenced not just by the presence of H. pylori, but also by the complex interplay of its virulence factors, the host's immune response, and the gastrointestinal microbiome.\u003c/p\u003e \u003cp\u003eOur study findings revealed that 4.5% of patients had a history of continuous corticosteroid use for at least two weeks. Corticosteroid treatment is associated with an increased risk of gastrointestinal side effects such as gastritis, ulcers, and gastrointestinal bleeding. The estimated relative risk increase for gastrointestinal side effects with corticosteroid alone varies between 1.1 and 1.5 times accroding to Liu et al\u0026rsquo;s study. Concurrent use of corticosteroids and NSAIDs notably increases gastrointestinal event risks (28).\u003c/p\u003e \u003cp\u003eAnother finding of our research is that 67% of patients with perforated gastric ulcers had been taking NSAIDs. The excessive use of NSAIDs in these patients can be attributed to an increase in musculoskeletal pain and cardiovascular diseases associated with aging (refer to Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). NSAIDs have been identified as a potential risk factor for mortality following upper gastrointestinal bleeding, primarily caused by peptic ulcers, in various studies, including those by Sibilia and colleagues (29), Ben-Menachem and colleagues (30), and Straube and colleagues (31). However, Wu et al.'s study (32), involving 52,161 patients, revealed that regular NSAID use, particularly in patients with H. pylori-associated gastric ulcers, significantly lowered the risk of gastric cancer. This was evident in their observation that patients who never used NSAIDs had a higher risk of gastric cancer, while regular NSAID users showed a notably reduced risk. This is in line with our study's result; our study found that 66.9% of patients with perforated stomach ulcers were NSAID users, and importantly, none of these patients exhibited signs of malignancy in their gastric biopsies. This absence of malignancy in NSAID users with gastric ulcers aligns with and supports Wu et al.'s findings, suggesting a protective role of NSAIDs against the development of gastric cancer, especially in the context of H. pylori infection.\u003c/p\u003e \u003cp\u003eIn contrast, Li et al. (33) explored the impact of non-aspirin (NA-NSAIDs) on gastric cancer development in a large cohort of over 92,000 H. pylori-infected patients who had undergone H. pylori eradication therapy. This large-scale, territory-wide study used a time-dependent analysis to address potential biases. Contrary to previous meta-analyses that suggested a beneficial effect of NSAIDs (including both aspirin and NA-NSAIDs) on gastric cancer prevention, this study found that the use of NA-NSAIDs was not associated with a decreased risk of developing gastric cancer. This finding presents a contrasting perspective to the commonly held view of NSAIDs' protective role in gastric cancer development.\u003c/p\u003e \u003cp\u003eInterestingly, 59% of patients with gastric ulcer perforation had a history of substance abuse. The study by Salemi et al. (34) also has shown a significant link between peptic ulcers and smoking. It seems that the mechanisms of tobacco and drug use in causing peptic ulcers are similar, and the continuation of these habits may lead to ulcer perforation. Smoking increases acid production and decreases bicarbonate and prostaglandin production, according to Ramakrishnan et al. (22). This can delay the healing of duodenal and gastric ulcers.\u003c/p\u003e \u003cp\u003eIn a study by Paragomi et al. (35) which investigated the association between PUD and Gastric Cancer by incorporating data from 11 case-control studies within their consortium, a significant link was established between gastric ulcers and an elevated risk of gastric cancer. However, no such association was observed with duodenal ulcers. Notably, it is essential to consider that pre-pyloric ulcers, a subtype of GU, carry the highest risk of perforation. Furthermore, the higher risk of non-cardia GC in patients with GU underscores the importance of specific and accurate diagnostic methods such as biopsy or gastroscopy, especially in cases with gastric ulcers. While our study did not investigate the location of the ulcer or the number of biopsy samples, these aspects could pave the way for future research. The decision to perform a biopsy can be made based on the doctor's preference, the patient's condition, and the availability of resources.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this study, we exclusively examined patients with perforated pre-pyloric gastric ulcers and found no evidence of malignancy or gross masses in the collected samples. These findings suggest that biopsy procedures may be unnecessary for patients presenting with pre-pyloric gastric ulcers in the absence of any indicators of malignancy or noticeable masses. Therefore, we recommend more selective criteria for biopsies in future studies, potentially reducing the number of unnecessary invasive procedures for patients with similar presentations.\u003c/p\u003e\n\u003ch3\u003eResearch Limitations\u003c/h3\u003e\n\u003cp\u003eThe duration of gastric ulcer affliction was not examined and the study did not investigate cigarette smoking diet habits and presence of H. pylori.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eRecommendations for Future Research\u003c/h2\u003e \u003cp\u003eIt's suggested that a study be conducted to explore the risk factors for perforation in patients with gastric ulcers. Given the number of samples in this study, it is recommended that future research involve more extensive sample sizes and include follow-up of patients after treatment and the healing of perforated ulcers.\u003c/p\u003e \u003c/div\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the ethics committee of Tehran University of Medical Sciences (TUMS) (ethics code IR.TUMS.SINAHOSPITAL.REC.1400.079.), and followed the guidelines of the Helsinki Declaration and the Iranian Ministry of Health and Medical Education.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe participants have given their consent for the publication of their data and study findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted without any funding or involvement from external sources.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study\u0026apos;s conception and design. Material preparation, data collection, and analysis were performed by Hadi Ahmadi Amoli, Mohamadhosein Imanipour, and Reza Hajebi. The first draft\u0026nbsp;and main text\u0026nbsp;of the manuscript was written and revised critically by Soha Mohammadi and Nima Taghizadeh, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge the contributions and support provided by medical and nursing staff of Sina hospital who have assisted in various aspects of this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eErgul E, Gozetlik EO. Emergency spontaneous gastric perforations: ulcus versus cancer. \u003cem\u003eLangenbeck's archives of surgery\u003c/em\u003e. 2009;394:643-646.\u003c/li\u003e\n\u003cli\u003eRavisankar P, Koushik O, Reddy A, KumarU AP, Pragna P. A detailed analysis on acidity and ulcers in esophagus, gastric and duodenal ulcers and management. \u003cem\u003eIOSR Journal of Dental and Medical Sciences (IOSR-JDMS)\u003c/em\u003e. 2016;15(1):94-114.\u003c/li\u003e\n\u003cli\u003eTarasconi A, Coccolini F, Biffl WL, et al. Perforated and bleeding peptic ulcer: WSES guidelines. \u003cem\u003eWorld Journal of Emergency Surgery\u003c/em\u003e. 2020;15(1):1-24.\u003c/li\u003e\n\u003cli\u003eAhmed M, Mansoor T, Rab AZ, Rizvi SAA. Risk factors influencing postoperative outcome in patients with perforated peptic ulcer: a prospective cohort study. \u003cem\u003eEuropean Journal of Trauma and Emergency Surgery\u003c/em\u003e. 2022:1-6.\u003c/li\u003e\n\u003cli\u003eWeledji EP. An overview of gastroduodenal perforation. \u003cem\u003eFrontiers in Surgery\u003c/em\u003e. 2020;7:573901.\u003c/li\u003e\n\u003cli\u003eAbbass A, Khalid S, Boppana V, Hanson J, Lin H, McCarthy D. Giant gastric ulcers: an unusual culprit. \u003cem\u003eDigestive Diseases and Sciences\u003c/em\u003e. 2020;65:2811-2817.\u003c/li\u003e\n\u003cli\u003eAnania G, Campagnaro A, Marchetti F, Resta G, Cirocchi R. Perforated Gastroduodenal Ulcer. 2021:129-139.\u003c/li\u003e\n\u003cli\u003eKarabulut K, Din\u0026ccedil;er M, Liman RK, Usta S. Non-operative management of perforated peptic ulcer: A single-center experience. \u003cem\u003eUlus Travma Acil Cerrahi Derg\u003c/em\u003e. 2019;25(6):585-588.\u003c/li\u003e\n\u003cli\u003ePouli S, Kozana A, Papakitsou I, Daskalogiannaki M, Raissaki M. Gastrointestinal perforation: clinical and MDCT clues for identification of aetiology. \u003cem\u003eInsights into Imaging\u003c/em\u003e. 2020;11(1):1-19.\u003c/li\u003e\n\u003cli\u003eAli A, Ahmed BH, Nussbaum MS. Surgery for peptic ulcer disease. \u003cem\u003eShackelford's Surgery of the Alimentary Tract, 2 Volume Set\u003c/em\u003e. Elsevier; 2019:673-701.\u003c/li\u003e\n\u003cli\u003eFelder SI, Barmparas G, Murrell Z, Fleshner P. Risk factors for failure of percutaneous drainage and need for reoperation following symptomatic gastrointestinal anastomotic leak. \u003cem\u003eAm J Surg\u003c/em\u003e. Jul 2014;208(1):58-64. doi:10.1016/j.amjsurg.2013.08.050\u003c/li\u003e\n\u003cli\u003eKumarasinghe MP, Bourke MJ, Brown I, et al. Pathological assessment of endoscopic resections of the gastrointestinal tract: a comprehensive clinicopathologic review. \u003cem\u003eModern Pathology\u003c/em\u003e. 2020;33(6):986-1006.\u003c/li\u003e\n\u003cli\u003eWan JJ, Fei SJ, Lv SX, et al. Role of gastroscopic biopsy of gastric ulcer margins and healed sites in the diagnosis of early gastric cancer: A clinical controlled study of 513 cases. \u003cem\u003eOncol Lett\u003c/em\u003e. Oct 2018;16(4):4211-4218. doi:10.3892/ol.2018.9156\u003c/li\u003e\n\u003cli\u003eMarusawa H, Jenkins BJ. Inflammation and gastrointestinal cancer: an overview. \u003cem\u003eCancer Lett\u003c/em\u003e. Apr 10 2014;345(2):153-6. doi:10.1016/j.canlet.2013.08.025\u003c/li\u003e\n\u003cli\u003eSancho-Poch F, Balanzo J, Ocana J, et al. An evaluation of gastric biopsy in the diagnosis of gastric cancer. \u003cem\u003eGastrointestinal endoscopy\u003c/em\u003e. 1978;24(6):281-282.\u003c/li\u003e\n\u003cli\u003eYang H, Wei B, Hu B. Chronic inflammation and long-lasting changes in the gastric mucosa after Helicobacter pylori infection involved in gastric cancer. \u003cem\u003eInflammation Research\u003c/em\u003e. 2021:1-12.\u003c/li\u003e\n\u003cli\u003eShirani M, Pakzad R, Haddadi MH, et al. The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis. \u003cem\u003eBMC Infectious Diseases\u003c/em\u003e. 2023;23(1):543.\u003c/li\u003e\n\u003cli\u003eButt J, Varga MG, Wang T, et al. Smoking, Helicobacter Pylori Serology, and Gastric Cancer Risk in Prospective Studies from China, Japan, and Korea. \u003cem\u003eCancer Prev Res (Phila)\u003c/em\u003e. Oct 2019;12(10):667-674. doi:10.1158/1940-6207.Capr-19-0238\u003c/li\u003e\n\u003cli\u003eWang XQ, Terry PD, Yan H. Review of salt consumption and stomach cancer risk: epidemiological and biological evidence. \u003cem\u003eWorld J Gastroenterol\u003c/em\u003e. May 14 2009;15(18):2204-13. doi:10.3748/wjg.15.2204\u003c/li\u003e\n\u003cli\u003eGaddy JA, Radin JN, Loh JT, et al. High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis. \u003cem\u003eInfect Immun\u003c/em\u003e. Jun 2013;81(6):2258-67. doi:10.1128/iai.01271-12\u003c/li\u003e\n\u003cli\u003eBhattarai S, Gyawali M, Regmi S. Prevalence of Gastric Cancers among Patients Undergoing Upper Gastrointestinal Endoscopies in a Tertiary Care Hospital in Nepal: A Descriptive Cross-sectional Study. \u003cem\u003eJNMA J Nepal Med Assoc\u003c/em\u003e. Jan 31 2021;59(233):65-68. doi:10.31729/jnma.5657\u003c/li\u003e\n\u003cli\u003eRamakrishnan K, Salinas RC. Peptic ulcer disease. \u003cem\u003eAm Fam Physician\u003c/em\u003e. Oct 1 2007;76(7):1005-12.\u003c/li\u003e\n\u003cli\u003eHearnshaw SA, Logan RF, Lowe D, Travis SP, Murphy MF, Palmer KR. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. \u003cem\u003eGut\u003c/em\u003e. Oct 2011;60(10):1327-35. doi:10.1136/gut.2010.228437\u003c/li\u003e\n\u003cli\u003eCheung J, Rajala J, Moroz D, Zhu Q, Stamm M, Sandha GS. Acetylsalicylic acid use in patients with acute myocardial infarction and peptic ulcer bleeding. \u003cem\u003eCan J Gastroenterol\u003c/em\u003e. Sep 2009;23(9):619-23. doi:10.1155/2009/509258\u003c/li\u003e\n\u003cli\u003eKumar S, Kumar A, Dixit VK. Direct detection and analysis of vacA genotypes and cagA gene of Helicobacter pylori from gastric biopsies by a novel multiplex polymerase chain reaction assay. \u003cem\u003eDiagn Microbiol Infect Dis\u003c/em\u003e. Dec 2008;62(4):366-73. doi:10.1016/j.diagmicrobio.2008.07.014\u003c/li\u003e\n\u003cli\u003ePiazuelo MB, Correa P. Gastric c\u0026aacute;ncer: Overview. \u003cem\u003eColomb Med (Cali)\u003c/em\u003e. Jul 2013;44(3):192-201.\u003c/li\u003e\n\u003cli\u003eAlexander SM, Retnakumar RJ, Chouhan D, et al. Helicobacter pylori in Human Stomach: The Inconsistencies in Clinical Outcomes and the Probable Causes. \u003cem\u003eFront Microbiol\u003c/em\u003e. 2021;12:713955. doi:10.3389/fmicb.2021.713955\u003c/li\u003e\n\u003cli\u003eLiu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. \u003cem\u003eAllergy Asthma Clin Immunol\u003c/em\u003e. Aug 15 2013;9(1):30. doi:10.1186/1710-1492-9-30\u003c/li\u003e\n\u003cli\u003eSibilia J, Ravaud P, Marck G. [Digestive and hemorrhage complications of low-dose aspirin]. \u003cem\u003ePresse Med\u003c/em\u003e. Nov 22 2003;32(37 Pt 2):S17-28. Les complications digestives et h\u0026eacute;morragiques de l'aspirine \u0026agrave; faible dose.\u003c/li\u003e\n\u003cli\u003eBen-Menachem T, Dominitz JA. Acute upper gastrointestinal hemorrhage in an elderly woman taking aspirin and clopidogrel. \u003cem\u003eClin Gastroenterol Hepatol\u003c/em\u003e. Aug 2011;9(8):649-52. doi:10.1016/j.cgh.2011.03.022\u003c/li\u003e\n\u003cli\u003eStraube S, Tram\u0026egrave;r MR, Moore RA, Derry S, McQuay HJ. Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. \u003cem\u003eBMC Gastroenterol\u003c/em\u003e. Jun 5 2009;9:41. doi:10.1186/1471-230x-9-41\u003c/li\u003e\n\u003cli\u003eWu CY, Wu MS, Kuo KN, Wang CB, Chen YJ, Lin JT. Effective reduction of gastric cancer risk with regular use of nonsteroidal anti-inflammatory drugs in Helicobacter pylori-infected patients. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. Jun 20 2010;28(18):2952-7. doi:10.1200/jco.2009.26.0695\u003c/li\u003e\n\u003cli\u003eLi B, Cheung KS, Wong IY, Leung WK, Law S. Nonaspirin nonsteroidal anti-inflammatory drugs and gastric cancer risk after Helicobacter pylori eradication: A territory-wide study. \u003cem\u003eCancer\u003c/em\u003e. Jun 1 2021;127(11):1805-1815. doi:10.1002/cncr.33412\u003c/li\u003e\n\u003cli\u003eSalemi Z, Kamali Pooya S, Ghasemi M. Secretor Status and Some Risk Factors in Duodenal Ulcer, Gastric Ulcer, and Gastric Cancer. Original Atricle. \u003cem\u003eJournal of Arak University of Medical Sciences\u003c/em\u003e. 2013;16(3):0-0.\u003c/li\u003e\n\u003cli\u003eParagomi P, Dabo B, Pelucchi C, et al. The Association between Peptic Ulcer Disease and Gastric Cancer: Results from the Stomach Cancer Pooling (StoP) Project Consortium. \u003cem\u003eCancers (Basel)\u003c/em\u003e. Oct 7 2022;14(19)doi:10.3390/cancers14194905\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"peptic ulcer perforation, gastric ulcer, peptic ulcer, gastric cancer","lastPublishedDoi":"10.21203/rs.3.rs-3850897/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3850897/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003ePeptic ulcers, common digestive system disorders, often lead to perforation, which is associated with high mortality. Given the potential for underlying malignancy in gastric ulcers and perforations, this study focuses on assessing the frequency of cancer in gastric biopsies of patients with perforated pre-pyloric gastric ulcers.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis cross-sectional study involved 175 patients of all ages, both genders, with perforated pre-pyloric gastric ulcers in 2021\u0026ndash;2022, who underwent emergency laparotomy surgery and with a definitive diagnosis of gastric ulcer perforation. A full-thickness sample was taken from the margin of the perforated pre-pyloric gastric ulcer for pathological examination to detect gastric malignancy.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe patients' average age was 65.69 years, with a median of 65 years. All histopathological examinations of the gastric ulcer samples indicated benign conditions. Among the patients, 54.3% had a history of gastric ulcers, 37.7% had diabetes, 25.7% had hypertension, and 25.7% had both. Additionally, 1.7% suffered from chronic kidney failure, 1.1% from chronic liver failure, and 0.8% had other conditions like cardiovascular diseases. In total, 4.6% patients had a history of corticosteroid use, 66.9% patients had a history of NSAID use, and 58.9% patients had drug addiction.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur study found no signs of cancer in the biopsies of patients with perforated pre-pyloric gastric ulcers; all cases showed benign pathology. This suggests that using gastric ulcer perforation alone as a reason for biopsy may need more investigation to ensure its accuracy and relevance.\u003c/p\u003e","manuscriptTitle":"Occurrence of Malignancy in Biopsy Specimens from Patients with Perforated Pre-pyloric Gastric Ulcers ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-12 17:58:32","doi":"10.21203/rs.3.rs-3850897/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"021fd703-8237-4ca8-be43-e30470d0a9fd","owner":[],"postedDate":"January 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-13T20:59:30+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-12 17:58:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3850897","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3850897","identity":"rs-3850897","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}